1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → N-((tetrahydro-2H-pyran-4-yl)methyl)-2-(4-(1-(((4-(trifluoromethyl)benzyl)oxy)imino)propyl)phenoxy)acetamide

HRID 68309Notes

Reaction equation

HRID 68309 reaction equation
[F:1][C:2]([F:27])([F:26])[C:3]1[CH:25]=[CH:24][C:6]([CH2:7][O:8][N:9]=[C:10]([C:13]2[CH:23]=[CH:22][C:16]([O:17][CH2:18][C:19]([OH:21])=O)=[CH:15][CH:14]=2)[CH2:11][CH3:12])=[CH:5][CH:4]=1.[O:28]1[CH2:33][CH2:32][CH:31]([CH2:34][NH2:35])[CH2:30][CH2:29]1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.CN(C1C=CN=CC=1)C.C1C=CC2N(O)N=NC=2C=1>[O:28]1[CH2:33][CH2:32][CH:31]([CH2:34][NH:35][C:19](=[O:21])[CH2:18][O:17][C:16]2[CH:15]=[CH:14][C:13]([C:10](=[N:9][O:8][CH2:7][C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:26])([F:1])[F:27])=[CH:25][CH:24]=3)[CH2:11][CH3:12])=[CH:23][CH:22]=2)[CH2:30][CH2:29]1

Participants

7

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27732104-AminomethyltetrahydropyranHCID 743706342-(4-(1-(((4-(Trifluoromethyl)benzyl)oxy)imino)propyl)phenoxy)acetic acid

Product 1

HCID 76528397N-((tetrahydro-2H-pyran-4-yl)methyl)-2-(4-(1-(((4-(trifluoromethyl)benzyl)oxy)imino)propyl)phenoxy)acetamideYield 57.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 757711-HydroxybenzotriazoleCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of the product of step 4 (23 g, 0.0602 moles) in DMF (69 mL), (tetrahydro-2H-pyran-4-yl)methanamine (7.6 gm, 0.0662 moles), HOBT (50 mg, catalytic amount), EDC.HCl (17.5 g, 0.0903 moles) and DMAP (50 mg, catalytic amount) were added and reaction mixture was srirred at 25° C. for 16 hours. The reaction mixture was poured into ice cold water and extracted with ethyl acetate. The combined ethyl acetate extract was washed with water & brine, dried over sodium sulphate and evapourated under reduced pressure. The crude product was purified by coloumn chromatography using ethyl acetate:Hhexane (1:1) as eluent to yield 16.5 g (57%) of product as white solid. 1H NMR: DMSO-d6 δ 1.10 (t, J=6.6 Hz, 3H), 1.13-1.16 (m, 2H), 1.46-1.49 (m, 2H), 1.61-1.70 (m, 1H), 2.74 (q, J=7.6 Hz, 2H), 3.01 (t, J=6.6 Hz, 2H), 3.17-3.23 (m, 2H), 3.78-3.81 (dd, J=11.4 & 2.6 Hz, 2H), 4.51 (s, 2H), 5.26 (s, 2H), 6.96 (dd, J=6.8 & 2.0 Hz, 2H), 5.57-5.61 (m, 4H), 7.72 (d, J=8.0 Hz, 2H), 8.10 (t, J=6.0 Hz, NH).

Workup

  1. customreaction mixture
  2. additionThe reaction mixture was poured into ice cold water
  3. extractionextracted with ethyl acetate
  4. extractionThe combined ethyl acetate extract
  5. washwas washed with water & brine
  6. dry with materialdried over sodium sulphate
  7. customThe crude product was purified by coloumn chromatography

Sources & evidence

ORD record
ord-2d6be4d2aa084c3fa20401b2d6bb1615
Source dataset
uspto-grants-2014_09
Patent number
US08822414B2

Reaction notes

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